There is growing evidence that gastroesophageal disease is influenced by the esophageal microbiome, and that commensal bacteria of the oropharynx, stomach, and colon are thought to have a role in modulatiing pathogenesis. These emerging hypotheses are based on observed changes in the composition of the esophageal flora, notably, repeated observations: 1. There is an abundance of gram-positive bBacteria in the healthy esophagus. are more gram positive prevalent 2. The esophageal bacterial population becomes increasingly gram negative with disease progression. Associated with this shift to a more gram negative prevalence is an increase in the potential for the presence of antigenic lipopolysaccharide (LPS). The immunoreactivity of LPS endotoxin thought to promote susceptibility to inflammation and disease.
The pathogenesis of the more common diseases of the esophagus e.g. gastroesophageal reflux disease (GERD), esophageal dysmotility (achalasia), eosinophilic esophagitis (EoE), Barrett’s esophagus (BE), and esophageal cancer, are well-established. Emerging data suggest however, that these are all characterized by an immune-mediated inflammatory cascade, propogated by a dysbiotic state. Thereby, the ability of the healthy “normative state” to protect against foreign bacteria is compromised. This dysbiosis thereby can create adverse inflammatory or immunoregulatory responses with progression of disease.
In the normal healthy state, the esophageal microbiome is constituted in-part, by a multitude of gram positive bacteria, many of which produce antibacterial peptides called bacteriocins. Bacteriocins are selective and used to maintain population integrity by killing off foreign bacteria. When the “normative biome” is interrupted (e.g. antibiotics, medications, diet, environmental factors), the constitutional changes may allow a more hospitable imbalance favoring the proliferation of opportunistic pathogens. Therefore it seems rational that defining, perhaps that defining, perhaps cultivating, a protective bacterial community that could help prevent or mitigate inflammatory diseases of the esophagus. Furthermore, in conjunction with evidence demonstrating that some bacteriocins are cytotoxic or antiproliferative toward cancer cell lines, further exploration might provide a rich source of effective peptide-based drug targets.
Therapeutic options targeting the microbiome, including prebiotics, probiotics, antibiotics and bacteriocins, have been studied, albeit the attributable effects on the esophagus for the most part, have been unrecognized by clinicians. This review focuses on the current knowledge of the involvement of the microbiome in esophageal diseases (most notably GERD/Barrett’s esophagus/esophageal cancer) and identifies emerging new concepts for treatment.
Hepatocellular carcinoma (HCC) is characterized by high morbidity, high recurrence, and high mortality rates. In China, the morbidity of HCC is fifth among all malignant tumors and HCC is the third most common cause of cancer-related deaths. Most HCC patients also have liver cirrhosis. Surgery is the sole curative method for HCC; however, many patients are diagnosed with HCC during its advanced stages so radical resection can no longer be performed. Therefore, the proportion of patients who undergo radical hepatectomy is less than 30%. Patients with mildly advanced HCC cannot undergo hepatectomy and thus transcatheter arterial chemoembolization (TACE) and/or biological targeted therapy are alternative options. However, data on the effects of TACE therapy or biological targeted therapy are limited. Therefore, an investigation of multimodal and individualized treatments is critical to ensure the best treatment. In June 2018, we treated an advanced HCC patient with multiple metastases and right portal vein tumor thrombus. The patient exhibited partial remission after undergoing treatment with TACE and crizotinib capsules for 1 month. The case and a literature review are reported here.
Background: Like other viruses, the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) appears to be responsible for several autoimmune complications. The occurrence of autoimmune hemolytic anemia has been described in several case reports. This AIHA was also noticeable by the important number of blood transfusions required for COVID-19 (coronavirus disease 2019) patients. By investigating RBC coating autoantibodies, this article attempts to clarify the autoimmune aspect of the anemia in the context of SARS-CoV-2 infection.
Results: A large population of COVID-19 patients selected at Saint-Luc University Hospital showed an average of 44% DAT positivity. In this population, the intensive care patients were more prone to DAT positivity than the general ward patients (statistically significant result). The positive DAT appeared « transmissible » to other RBCs via COVID-19 DAT-positive patient’s plasma.
Conclusion: The strongest hypothesis explaining this observation is the targeting of cryptic antigens by autoantibodies in COVID-19 patients.
Introduction: Forty-six per cent children have allergic rhinoconjunctivitis (Allergologica 2005).
Working hypothesis: Ocular topical cyclosporine improves the quality of life for these patients.
Material, methods, design: 2-year prospective study (2015-16), 40 patients with topical corticosteroids without improvement, followed 20 and 20 switched to corticosteroids cyclosporine 0.05%. Interview with Quality of Life Questionnaire in Children with rhinoconjunctivitis (PRQLQ) before and at the end of treatment. Mean age of 10.3 years with 60% male-40% female. Treatments were applied from January to March. There were 15 questions divided into two blocks. Children responded using a card with responses rated from zero (not bothered at all) to 6 (quite upset).
Results: Before the 100% reported that, the itching was very bothersome. In the group of 40 children, 80% showed symptoms of epiphora and 60% showed symptoms of ocular inflammation. 100% complained of significant discomfort in rubbing their eyes, 30% did not like to take medications. Headaches affected 20%. 100% stated that they cannot play normally. 80% showed decreased concentration in class.
Continuing with corticosteroids did not show statistically significant changes.
Patients with cyclosporine improved the results by 3 points, with decreased itching, tearing, swelling, pain, eye rubbing, medication and headaches. In the 2nd questionnaire there was limited variation in the results related to fatigue, malaise, and irritability but with substantially improved balance of sleep, insomnia and concentration at school.
Conclusion: Cyclosporine A is a cyclic polypeptide calcineurin inhibitor developed from the fungus Tolypocladium inflatum. The first dilution was 2% but it is currently used at a dilution of 0.05% and recent publications suggest nanosuspensions. Our study showed improvement in parameters related to symptoms, especially itching and lower improvement of psychological aspects, this achieves a better quality of life for children and more willingness to adhere to the treatment.
Inflammatory Bowel Disease (IBD)-associated arthritis is called Enteropathic Arthritis (EA) which is classified among the group of Spondyloarthritis (SpA), because its presentation is variable. The current trend is to classify them as autoinflammatory rather than autoimmune diseases, since no antibodies have yet been identified. The study of biomarkers (BM) will help us with early identification and hence, to provide treatment in the early stages, prior to radiographic progression, which will enable prompt identification of the disease phenotype. 42 patients diagnosed with IBD were included, of which 48% were females; the mean age of the study group was 48.12 ± 5.02 (95% CI). The average time of evolution of disease was 37.57 ± 14.28 months; most patients referred to the rheumatologist had a diagnosis of ulcerative colitis (83%). According to our analysis, we were able to determine that the three most significant variables influencing the development of sacroiliitis were: Lactoferrin, ANCA and HLA B27 (p < 0.5). The variable that can be ruled out because of its almost neglectable contribution was fecal calprotectin.
Alberta Cappelli*, Silvio Laureti, Nunzia Capozzi, Cristina Mosconi, Francesco Modestino, Giuliano Peta, Silvia Lo Monaco, Antonio Bruno, Giulio Vara, Caterina De Benedittis, Paolo Gionchetti, Fernando Rizzello, Gilberto Poggioli and Rita Golfieri
Published on: 5th October, 2020
Purpose: Percutaneous abscess drainage (PAD) is the first-line approach for abscess in Crohn’s disease (CD) since it procrastinates or avoids surgery especially in postoperative abscesses [within 30 days post-operative (p.o.)]. We retrospectively evaluated the effectiveness, complications and outcome after PAD in postoperative and spontaneous abscesses and factors influencing the outcomes.
Methods: We performed PAD in 91 abscesses, 45 (49,5%) postoperative and 46 (50,5%) spontaneous.
We defined the overall success (OS) as clinical (CS) and technical success (TS) when imaging documented the resolution of the abscess with no surgery within 30 days.
Conversely, patients without abscess at the time of surgery, were considered as TS but clinical failure (CF).
We also analyzed the overall failure (OF) defined as CF with or without technical failure (TF).
Overall technical success (OTS) was OS plus TS. Complications were classified as major and minor according to the Interventional Radiology Criteria.
Results: In postoperative abscesses we found 91% OS, 9% OF, no TF and 100% OTS.
In spontaneous abscesses we found 33% OS, 67% OF, 6.4% TF, 95,6% OTS.
A total abscess resolution was achieved in 97,8% of patients. No major complication occurred; only 1 case of minor complication. Factors statistically influencing the outcome were postoperative vs spontaneous collections (OF: 9% vs. 67%, p < 0.0001), multiloculated vs uniloculated collections (OF: 38% vs. 1%, p < 0.0001) and upper abdominal vs lower location (OF: 13% vs. 25%, p <0.05).
Conclusion: Our data confirms the safety and effectiveness of PAD even in cases needing surgery within 30 days; most remarkable, PAD allows avoidance of early reoperation in almost all the patients with postoperative abscess.
Exposure to environmental chemicals is a potential cause for the rapid increase in the prevalence of allergic asthma over the last few decades. The production of the environmental estrogen bisphenol A, the monomer of polycarbonate plastics, has increased rapidly over the last 50 years, such that bisphenol A is one of the most highly produced chemicals. It is detectable in the urine of the vast majority of the human population. While the relationship between the increase of bisphenol A in our environment and the prevalence of asthma does not prove a cause and effect relationship, it provides a strong rationale for experiments that have tested the hypothesis. Because of its small molecular size and hydrophobicity, bisphenol A is easily transferred from the mother to the fetus, via the placenta and in breast milk.
We have reviewed all the publications available on medline on the human epidemiological studies of the early bisphenol A exposure on the development of allergic asthma and experimental studies using mouse model of the effects of early bisphenol A exposure on the development of asthma. There are eight human epidemiological studies and five mouse model studies currently published.
The human studies suggest that bisphenol A exposure in early life enhances the likelihood of developing asthma on at least one of the study groups. The effects of early bisphenol A exposure were observed as an enhanced development of asthma before adolescent in the animal model.
Background:While recognition and documentation of true drug allergy is critically important, most physicians acknowledge that its prevalence is likely overestimated, often on the basis of historical, sometimes anecdotal evidence. Correct or not, once applied, drug allergy labels may result in altered, potentially inferior therapy, increased costs and prolonged hospitalisation.
Objective:Estimate the point prevalence, accuracy and symptomatology of self-reported drug allergy in a typical, large NHS Acute Trust adult inpatient population. In the subset with penicillin allergy (PA), estimate additional management costs from the use of alternative antibiotics and readmission rates in the previous 5 years.
Methods:Data on self-reported drug allergies were extracted from 440 adult inpatient prescription charts over a 4 month period. Where penicillin allergy (PA) was reported, alternative antibiotic regimens were recorded and their additional costs calculated. Hospital electronic records were used to assess readmission rates of PA patients.
Results:194/440 inpatients (44.5%) reported at least one drug allergy. Antibiotic allergy was most commonly reported (51%), followed by analgesic (23%) and antiemetic (12%) allergy. PA accounted for 76% of reported antibiotic allergy. The commonest reported symptoms were cutaneous (42%) and gastrointestinal (18%). Where antibiotic therapy was required for patients with PA to manage acute infections, Ciprofloxacin, Clarithromycin, Teicoplanin, Clindamycin and Cefuroxime were the most commonly employed alternatives. Extrapolation of these figures to include the entire Trust inpatient population suggested that the use of alternative antibiotics in PA patients incurred additional annual expenditure of £268,000. Further, 87% of PA patients had been admitted more than once in the preceding 5 years, with 74% requiring further courses of antibiotics during these admissions.
Conclusion:Self-reported drug allergy, and in particular PA, is common in hospital inpatient populations and, in addition to the potentially unnecessary hazards to individual patients resulting from the use of alternative antibiotics, results in a considerable additional financial burden to the healthcare system. This problem could be eliminated by the provision of a nationwide and equitable tertiary Allergy service.
Coronavirus infections have caused outbreaks in humans: SARS-COV ((Severe Acute Respiratory Syndrome) and MERS-CoV (Middle East Respiratory Syndrome) resulting in significant mortality and morbidity
Acute liver failure (ALF) in children is a severe disease with a high mortality rate. The current treatment strategies are still defective, with many cases die when liver transplantation is unavailable. The current protocol of steroids therapy improved the survival rate of hepatitis A virus (HAV)-related ALF. However, there is still a high mortality for non-HAV cases. Stem cell therapy (SCT) has been tried in experimental animals with ALF and in few adult studies with acute-on-chronic liver failure. No previous trials of SCT have been tested in children with ALF. The absence of SCT application in ALF in children could be due to some issues. These could be related to safety, sources, administration route, optimum dosage, efficacy, and survival. It is proposed that could be the future therapy if these obstacles have been well studied and solved.
Chronic asthma accounts for a significant amount of unscheduled office and emergency department (ED) visits. According to the latest World Health Organization statistics, asthma worldwide affects 300 million individuals and creates a substantial health burden by restricting the patient’s lifetime activities. Data estimate that asthma causes a loss of disability-adjusted life years over 150,000/year [1]. While most individuals with asthma can be controlled with current therapies, 5-10% of patients have difficult-to-control/refractory asthma. Severe or refractory asthma places a significant burden on the patient and often requires treatment with systemic glucocorticoids, which have significant side effects. The American Thoracic Society and the European Respiratory Society define refractory asthma as asthma that requires treatment with high-dose inhaled corticosteroids (ICS) plus a second controller and/or systemic corticosteroids to prevent it from becoming ‘‘uncontrolled’’ or asthma that remains ‘‘uncontrolled’’ despite this aggressive therapy. To fully meet this definition the diagnosis of asthma needs to be confirmed and comorbidities addressed as well. The above are considered major criteria for severe asthma and only one needs to be present for considering the diagnosis of refractory asthma [2]. For these reasons, clinicians must learn to identify and formulate additional diagnoses of “asthma imitators” [3]. One of the more common disorders associated with difficult-to-control asthma is vocal cord dysfunction (VCD) [4]. This disorder is known by many names, but current nomenclature endorsed by European and American societies correctly refers it as “Inducible Laryngeal Obstruction” (ILO) [5]. The following case demonstrates the importance of recognizing the clinical and spirometric features of ILO when asthma remains “refractory” to multiple therapies.
Seizure is clinical manifestation of sudden disruption of the normal electrical activity of cortical neurons. The brain electrical activity is periodically disturbed, alteration in neural cell integrity, increase in firing impulses and spread to adjacent normal neurons result in temporary brain dysfunction with alterations in consciousness, behavior or motor function. It may be triggered by illness, infection, stress, stroke, brain tumor, or the underlying cause may not completely understand. Status epilepticus (SE) is a medical emergency and requires prompt diagnosis and treatment. Treatment includes general support measures, drugs to suppress epileptic activity and relieving the underlying condition. Refractory SE requires admission to an intensive care unit (ICU) to allow adequate monitoring and support of respiratory, metabolic and hemodynamic functions and cerebral electrical activity. For SE treatment, benzodiazepines are the first line antiepileptic agents, and if benzodiazepines fail to control seizures, Phenytoin is usually indicated; Phenobarbital or Valproate may also be considered. For refractory SE, Propofol and Thiopental represent first line agents after careful assessment of potential risks. In refractory SE, general anesthesia may be required. There is currently no unique consensus for definite treatment option of RSE. In this review, the management protocol of seizure, assessment, monitoring, and different alternative therapy would be discussed.
Chest compression is the fundamental technique in cardiopulmonary resuscitation (CPR) in patients with cardiac arrest [1]. The quality and the early implementation of CPR are essential to improve the prognosis and the chances of restoring spontaneous circulation. In the literature, there are some articles about the poor quality of chest compression [2-4]. Therefore chest compression is as crucial as alerting the emergency services or early defibrillation in the survival chain. In accordance with the guidelines, chest compressions have to be performed continuously to improve the outcome [5]. However, the efficacy of manual chest compression diminishes over time with the fatigue of the provider (which appears within minutes of starting the procedure), and is impaired during transportation manoeuvres, which expose patients to unforeseen interruptions and a deterioration in the quality du massage in terms of power and rhythm. The efficacy of manual chest compression has been reported to fall by 20% per minute [6,7]. Mechanical chest compression overcome this problem of operator fatigue by ensuring constant efficacy in terms of both quality and quantity. Even though current data show no difference between manual chest compression and automated systems in terms of survival, haemodynamic studies in animal models have shown that mechanical techniques are more effective [8].
Allergen immunotherapy (AIT) is the unique curative treatment to help allergic patients to get over their allergies. With a personalized approach, AIT is the best example of precision medicine. After a century of intensive studies and innovative discoveries, allergists have in their hands many tools to orchestrate the best strategy to re-educate the hypersensitive immune systems that decrease the quality of life of their patients. This review describes both the historical and the promising acquisitions in this field, focusing the biochemical and Bioengineering tools that render an allergen more suitable for a secure, convenient and effective immunotherapy.
This review examines of the concept of a defective chloride channel in epithelial cells being a major cause of cystic fibrotic pathophysiology. The central concept of the defective chloride ion channel paradigm is that faulty CFTR protein or failed delivery of CFTR protein to the mucosal membrane of epithelial cells is the basis of cystic fibrosis. Defective placement or function of CFTR prevents hydration of bronchial mucus that is normally caused by epithelial cells; these are capable through chloride ion secretion of transporting fluid to the mucosal surface. This concept relies heavily on a paradigm taken from intestinal physiology-namely that the intestinal epithelial cell secretes chloride ion and fluid and that this has conferred heterozygote selective advantage in carriers of the cystic fibrosis gene. This present review examines the evidence for that hypothesis and assembles evidence from past studies that it is the smooth muscle cell that is of greater relevance. This review does not aim to provide an overview of current research into cystic fibrosis. The intention is to provide an overview of past research that led to the concept of a failure of epithelial cells to hydrate bronchial mucus because of compromised CFTR function. It is important to present all past evidence for aspects of the chloride secretion hypothesis and its associated heterozygote advantage concept so that the important evidential milestones can be re-assessed.
Background: The use of brain magnetic resonance imaging (MRI) for evaluation of neurological disorders has increased in the past two decades. This has led to an increased detection of incidental findings on brain MRI. The most common of these asymptomatic abnormalities are white matter lesions that are interpreted as demyelinating based on radiological criteria. However, in the absence of associated clinical symptoms suggestive of multiple sclerosis (MS), a definite diagnosis of MS can’t be made in patients with these incidental white matter lesions. These patients are diagnosed as CIS (clinically isolated syndrome) and RIS (radiologically isolated syndrome).Using the revised McDonald criteria now allows some patients who would have been diagnosed with CIS to be diagnosed as having MS before a second episode.
Method: Sixty one patients, 40 females and 21 males, age ranged between 15 years and 58 years, were included in our study. In addition to a detailed medical and neurological history and examination, CSF and blood analysis for oligoclonal bands and IgG index were performed for all patients.
Result: 41 patients had positive oligoclonal bands and IgG index. After clinical, MRI results and laboratory results 44 (72.1%) were diagnosed CIS and 17 (27.9%) were RIS.
Conclusion: Diagnosis of MS not depend only on MRI finding but need clinical and laboratory work up including CSF and blood analysis for oligoclonal bands and IgG index to confirm diagnosis.
Background: Multiple sclerosis (MS) is an autoimmune disorder of the central nerve system (CNS), which affects the brain and spinal cord. Experimental autoimmune encephalomyelitis (EAE) is the most commonly applied experimental model for studying the MS. The aim of this study was to determine the effects of Sesamum indicum seeds oil on Experimental Autoimmune Encephalomyelitis (EAE) in mice.
Methods: Sesame oil was administrated intraperitoneally three days before immunization. IFN-γ, IL-10, IL-17 and TGF-β levels and mRNA expression in supernatant of and within cultured mononuclear cells were assessed.
Results: According to our results, sesame oil treated mice demonstrated significant disease severity reduction (P=0.01 and 0.001, respectively). Treated EAE mice also represented statistically significant delay in the onset of symptoms in comparison with control group. The average IFN-γ levels and mRNA of sesame oil treated EAE mice were less than untreated EAE group. IL-10 and TGF-β levels and mRNA did not differ significantly in sesame oil treated EAE mice in comparison to untreated EAE group. IL-17 levels and mRNA were also found to be decreased significantly in treated mice in comparison to untreated mice.
Conclusions: Even thoughTH1 and TH17 cells through secretion of IFN-γ and IL-17, respectively, are involved in the pathogenesis of multiple sclerosis and EAE, but IL-10 has been shown to exhibit suppressive effects on these disorders. It can be concluded that sesame oil is able to induce TH2 and TH17-related immune responses and suppress TH1 type in EAE
This study describes chemotherapy exposure, healthcare utilization, overall survival (OS) and progression-free survival (PFS) among patients diagnosed with chronic lymphoid leukemia (CLL). Newly diagnosed CLL patients who received chemotherapy were selected from the Eindhoven Cancer Registry between 1998-2011, linked on a patient-level to the PHARMO Database Network including data on in- and out-patient drug dispensings, hospitalizations and clinical laboratory measurements. Chemotherapy was classified in regimens of use based on chemotherapy combinations. OS and PFS were determined after diagnosis and after chemotherapy. Healthcare utilization was assessed in the year before diagnosis and in the year after chemotherapy.
In total, 125 CLL patients received chemotherapy: 52 patients (42%) started chemotherapy within 6 months and 73 patients (58%) started chemotherapy ≥6 months after diagnosis. Mean (±SD) age was 67(±10) years and 68% was male. About 50% had one treatment line and about 25% two lines of treatment. Chlorambucil was the most common type of first line chemotherapy. Prior diagnosis, 44% were hospitalized for any cause and 94% had at least one drug dispensing. After chemotherapy, this was 43% and 98%, respectively. One-year survival rate after diagnosis was 94%. Median PFS after first treatment line was 17 months for patients starting within 6 months and 27 months for patients starting ≥6 months after diagnosis. In conclusion, most CLL patients receiving chemotherapy were treated with chlorambucil. One-year after initial diagnosis, 94% were still alive. Median PFS after first line chemotherapy ranged from 17 to 27 months, depending on the timing of chemotherapy.
Radiofrequency ablation is one of the most commonly used therapies for potentially curative small hepatocellular carcinoma. Although radiofrequency is usually a safe procedure, severe and potentially fatal complications can happen. This is a case of a 72 years old woman with cirrhosis secondary to Metabolic Associated Fatty Liver Disease (MAFLD), who presented recurrent hydrothorax after treating hepatocellular carcinoma (HCC) with radiofrequency ablation (RFA), and in which diaphragmatic perforation was subsequently diagnosed. We reviewed the differential diagnosis and management in a pleural effusion after a radiofrequency procedure. Although diaphragmatic perforation is an uncommon complication after RFA procedure, this case aims to help clinicians being aware of non-habitual complications.
Objectives: The study aims to assess the knowledge, attitude and practices of physicians who deal with pediatric age group SSTIs in reference to the Infectious Diseases Society of America (IDSA) guidelines on this regard that was published in 2014.
Background: Skin and soft tissue infections rank among the most frequent infections worldwide.
It is estimated that over 11 million ambulatory healthcare visits occur each year in US for skin and soft tissue infections due to Staphylococcus aureus (S. aureus) alone.
SSTIs are clinical entities of variable presentation, etiology and severity that involve microbial invasion of the layers of the skin and underlying soft tissues. SSTIs range from mild infections, such as pyoderma, to serious life-threatening infections, such as necrotizing fasciitis. One of the main challenges in managing SSTIs is to be able to identify those who need immediate inpatient intervention versus the more stable ones that can be manages in outpatient basis. In June of 2014, The Infectious Diseases Society of America (IDSA) released evidence based guidelines that has nicely covered all aspects related to the management of SSTIs.
Method:An anonymous 20-item survey exploring knowledge, attitude and practices associated with diagnosis and management of skin and soft tissue infection was distributed to physicians of different levels of expertise (from residents to consultants) in the departments of Pediatrics, Emergency Medicine and Family Medicine in different governmental facilities in Al-Ain city which is one of the major cities in United Arab Emirates.
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